# Regulation of MLK3 by LATS

> **NIH NIH R15** · UNIVERSITY OF TOLEDO · 2020 · $158,066

## Abstract

Abstract
Mixed lineage kinase 3 and 4 are mitogen-activated protein kinases (MAPKs) that regulate MAPK
signaling pathways, and mediate transmission of signals from cell surface receptors to the
nucleus. MLK3 and MLK4 have important functions in invasion and migration of ovarian and
breast cancer cells. Epithelial mesenchymal transition (EMT) is the process by which epithelial
cells lose cell polarity and adhesion properties and acquire the migratory and invasive
characteristics of mesenchymal cells. Aberrant activation of EMT can contribute to cell
transformation and cancer progression. Understanding how EMT is regulated is important for
development of new cancer treatments. Due to their functions in cellular transformation, we
hypothesized that MLK3 and MLK4 could be important regulators of the EMT process in ovarian
cancer cells. Our preliminary findings using siRNA knockdown of MLK3 and MLK4 in SKOV3
ovarian cancer cells indicate that loss of MLK3 or MLK4 affects the levels of EMT markers, E-
cadherin and vimentin. We propose that MLK3 and MLK4 are important modulators of EMT, and
when aberrantly regulated in ovarian cancer cells, promote EMT progression, invasion and
tumorigenesis. In the current study, we will investigate the mechanisms by which MLK3 and MLK4
regulate the expression of key EMT markers, and control ovarian cancer spheroid formation and
invasion.

## Key facts

- **NIH application ID:** 10056321
- **Project number:** 3R15CA241898-01S1
- **Recipient organization:** UNIVERSITY OF TOLEDO
- **Principal Investigator:** Deborah N Chadee
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $158,066
- **Award type:** 3
- **Project period:** 2019-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10056321

## Citation

> US National Institutes of Health, RePORTER application 10056321, Regulation of MLK3 by LATS (3R15CA241898-01S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10056321. Licensed CC0.

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